Hazard evaluation for complex mixtures: relative comparisons to improve regulatory consistency.

The traditional "absolute decision-making" process used by federal regulatory agencies to derive permissible exposure concentrations for hazardous substances is initiated by an evaluation of the "weight-of-evidence" that a substance is a potential human carcinogen. Subsequent conservative procedures applied variably to noncarcinogens and carcinogens yield exposure limits for individual substances based on "data-sparse, model-intensive" techniques which may lack consistency and have difficulty directly addressing the hazards from complex mixtures. This paper describes how a "relative decision-making" technique applicable to complex mixtures can supplement the "absolute" approach currently used. Estimates obtained through this "data-intensive, model-sparse" technique may be evaluated by comparisons to estimates representing a range of hazards "generally regarded as safe" derived through analyses of chlorinated drinking water, cigarette smoke condensate, and other common human exposures. Comparisons are also used to evaluate the relative degree of consistency in risk estimates between 58 suspect human carcinogens analyzed by the U.S. Environmental Protection Agency Carcinogen Assessment Group and by the authors.